A meta-analysis is usually grounded on the assumption that an aggregation of multiple, well-conducted studies can provide significant information that may not be evident by taking each study individually. Essential to this assumption is the premise that those studies included in the meta-analysis be scientifically rigorous in themselves. Unfortunately, this is almost never the case. The great utility of the meta-analysis in the clinical literature is such that there have emerged a series of standards for how to conduct such analyses, such as controlling for bias, controlling for variability, etc. These seldom include actual assessment of the scientific quality of the studies, as this is harder to standardize. Consequently, there is a preponderance of meta-analyzes that come to conclusions that are simply not justified, because the studies themselves were not scientifically rigorous.
I believe this applies to the situation of ivermectin, and it just so happens that this is the thrust of the point raised in the Nature article cited here.
Learning how to filter literature is non-trivial and I don't think very many people do it successfully. I've found the best thing is to take a group of aggressive smart grad students and have them tear every paper apart until I'm convinced there are no basic technical errors, and the conclusion is supported by the evidence. Then and only then, would I care that the methods were incomplete because I'd be ready to run a replication experiment, and many of my replications failed because the methods section was not sufficient (missing steps, misleading instructions, challenging step).
That's a pretty passable simplification of meta-analysis studies.
Often it is impractical to perform large studies. Partially by logistics and often by funding. But if there are lots of smaller studies you can aggregate the data to check for overall significant results. But mainly they are helpful to give a "survey" of the current research instead of having to link to 10 different studies and hope someone else sorts out what the data says.
But as you point out, there are two major flaws in the assumptions. First, that the scientific procedure is sound. Secondly, that the data is handled properly, and thus you can take the summary and back out the underlying data.
Unfortunately trying to fix the first is really, really hard.
The second is somewhat mitigatable. As the Nature article suggests, you could publish the underlying data (anonymized of course). This would help in two ways. First, the meta-analysis could check for confounding variables to control across all of the data. The second major one is it would help people spot fraudulent data.
However, as anyone who handles datasets knows, publishing and wrangling data into a useable state from multiple sources is a serious pain in the neck. Plus a lot of concerns about how de-anonymized the data would be. As we've known, with enough metadata it can be used to identify individuals. And publicly publishing dais data would definitely allow for some serious sleuthing work to be done.
None of the study results were robust, but many of the study outcomes were positive. So they were counting up positive outcomes and saying that more often than not, it was evidence that Ivermectin was effective.
This is a good means of generating a hypothesis, but a bad means of generating a conclusion.
Most of these studies were not in any way controlled or comparable in their conditions, and some had a very low number of observations. It didn't seem plausible that the data could be aggregated together.
It will be very interesting to see the results of the larger RCTs underway. Regardless of the outcome there _has_ to be a lesson for at least some people who arrived at fervent conclusions about what a miracle/scam this particular drug is. Unfortunately it seems unlikely that it will be a lesson that endures.
https://www.hhs.gov/hipaa/for-professionals/privacy/special-...
Double-blind is important for a reason, researchers are exceedingly good at proving what they want to prove even if subconscious, can meta-analysis studies ever overcome this?
But given what we've seen with p-hacking, it seems like it could be good if people pre-registered their meta analyses before crunching the numbers.
Next, we determine how much weight to give each poll in our average. First, polls conducted by pollsters with higher FiveThirtyEight pollster ratings — a letter grade measuring how accurate and methodologically sound pollsters are — are given more weight
https://fivethirtyeight.com/features/how-were-tracking-joe-b...
I won't disagree with you that there are many poorly conducted meta-analyses. However, I think there's many well-done meta-analyses as well, and most importantly maybe meta-analyses aren't really different from anything else in life: some are good, some are bad, and many are in between.
One thing I've always argued is that meta-analyses have as a benefit a way of honing discussion around concrete specifics. The linked paper, for example, exists in part because there was a meta-analysis drawing attention to the literature at large. There's a decent chance that these studies would never be discussed if there wasn't a spotlight being pointed at the area.
With reviews, what happens is people pick and choose studies anyway, or don't, and then come to some subjective conclusion that's based on some unclear process. Meta-analysis makes all of this clear, and forces everyone to be absolutely explicit (or as explicit as can be) about how they're coming to their conclusions. If there's something wrong with it, then you can point to the specifics of that instead of going back and forth.
The problem with relying on definitive studies alone is that sometimes there will be more than one of them, or there won't be any definitive study, but many decently-done studies. Or the "definitive" study will have some controversial feature that doesn't clearly rule it out, but clouds the waters in a way that several smaller studies might draw attention to. Alternatively, there might be important heterogeneity across designs that illuminates moderating variables (like dose, or environmental context, or gender, or age, or whatever).
This paper is about meta-analysis of summary statistics, which to me is kind of bringing up a red herring. Statistically speaking if you can calculate the right summary statistics, the results should be the same as having the raw data. Issues about irregularities in results apply to raw as well as summary statistics; it also seems unrealistic to expect raw data in every case, and journals don't apply that standard either (that is, journals don't expect reviewers to reanalyze the data from scratch).
What's really needed is open data sharing, and scrutiny about studies that increases as the stakes of the results increase. I can speak to cases where I've been surprised at the state of the raw data, even in situations where the whole point of the study was to skeptically replicate a finding. Maybe for something like invermectin raw data analyses are appropriate. But it seems absurd to expect to throw out studies in the literature just because you don't have access to the raw data in every case.
There more studies you include, the greater the chance you'll get a bad one. If you look at where these meta-analyses often fail, you'll often see just a few "Bad" studies that end up corrupting their results.
You'd think the statistical tools they bring to bear in these would be resistant to this, but it appears to not be the case in several recent cases.
I will re-post some thoughts I have previously shared from John P.A. Ioannidis who is a professor of medicine and thoughtful critic of medical research. He often raises good points about trends in research and research ethics. His view is that meta-analyses are mass produced, redundant, misleading, and conflicted [1]!
One criticism of meta-analyses in [1], using anti-depressants as a case study: "the results of several meta‐analytic evaluations that addressed the effectiveness of and/or tolerability for diverse antidepressants showed that their ranking of antidepressants was markedly different. These studies had been conducted by some of the best meta‐analysts in the world, all of them researchers with major contributions in the methods of meta‐analysis and extremely experienced in its conduct. However, among 12 considered drugs, paroxetine ranked anywhere from first to tenth best and sertraline ranked anywhere from second to tenth best."
I like this quote because it highlights the conflict of interest and misleading-ness(or at least reproducibility problems) with meta-analyses. Antidepressants have a huge amount of primary research dedicated to them. They also have the attention of researchers experienced in meta-analysis. Yet, meta-analyses do not agree with each other (and in fact they strongly disagree with each other).
https://en.wikipedia.org/wiki/John_Ioannidis#COVID-19
> In an editorial on STAT published March 17, 2020, Ioannidis called the global response to the COVID-19 pandemic a "once-in-a-century evidence fiasco" and wrote that lockdowns were likely an overreaction to unreliable data.[14] He estimated that the coronavirus could cause 10,000 U.S. deaths if it infected 1% of the U.S. population, and argued that more data was needed to determine if the virus would spread more.[28][5][14] The virus in fact eventually infected far more people, and would cause more than 600,000 deaths in the U.S.[29][28][5] Marc Lipsitch, Director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health, objected to Ioannidis's characterization of the global response in a reply that was published on STAT the next day after Ioannidis's.[30]
> Ioannidis widely promoted a study of which he had been co-author, "COVID-19 Antibody Seroprevalence in Santa Clara County, California", released as a preprint on April 17, 2020. It asserted that Santa Clara County's number of infections was between 50 and 85 times higher than the official count, putting the virus's fatality rate as low as 0.1% to 0.2%.[n 1][32][29] Ioannidis concluded from the study that the coronavirus is "not the apocalyptic problem we thought".[33] The message found favor with right-wing media outlets, but the paper drew criticism from a number of epidemiologists who said its testing was inaccurate and its methods were sloppy.
Okay then.
Nothing like spending a career picking apart people's research and then generating absolutely garbage research outside your field of expertise, that is widely criticized by people who are actually the experts in that field...as being inaccurate and sloppy.
COVID hit, dude went all Don Quixote seeing conspiracies everywhere, and then generated a paper that suited his personal biases...
It's worse than that; if you're reading individual papers without the context of the larger body of research in a domain, you're setting yourself up to get a distorted view of the world.
Peer review isn't magic; peer reviewed papers can still have errors, oversights, mistakes, outright fraud, or just get unlucky in how random chance played out. Peer review just filters out the obviously fraudulent or flawed papers so that only three reviewers have to spend an afternoon reading and understanding why they are useless, and not a thousand journal subscribers.
There's nothing wrong with following scientific developments as a layperson, but you shouldn't make the mistake of thinking because you read something in a published, peer-reviewed paper -- even one in a prestigious, well-respected journal like Science or Nature -- that it must be true.
The troubling thought is that in a field as complex and poorly understood as the intersection of virology with immunology at scale in the middle of a pandemic, the Experts are not much more informed than the layperson. I have yet to hear a single Expert showing even a tiny sliver of epistemic humility.
https://americasfrontlinedoctors.org/treatments/how-do-i-get...
peer review doesn't really mean as much as most people think and the paper was circulated by people who very well knew the difference and might have been circulating it precisely because of it.
Umm, wat?!
The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians.
Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs.
The evidence for IVM as a treatment for covid (and many other viruses) is quite strong.
There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake.
The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications.
Do you not thin that this incentive influences what gets into the news?
Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/
"In a study demonstrating the in vitro antiviral activity of ivermectin, upon incubation of infected Vero/hSLAM cells with 5 μM ivermectin, there was an approximately 5000-fold reduction of viral RNA by 48 hours in ivermectin treated samples as compared with control. The IC50 of ivermectin was found to be approximately 2.5 μM. Ivermectin seems to act on IMPα/β1 and inhibits the nuclear translocation of SARS-CoV-2 (Caly L et al., 2020). Further in-silico studies are required to confirm this target of ivermectin in SARS-CoV-2. The concentrations of 2.5 and 5 μM correspond to plasma concentrations of 2190 and 4370 ng/mL, respectively. These concentrations are 50–100 times the peak plasma concentration achieved with the 200 μg/kg of ivermectin (the US Food and Drug Administration recommended dose for treatment of onchocerciasis) (Chaccour C et al., 2017). Even with a dose 10 times greater than this dose (i.e., 2000 μg/kg), a peak plasma concentration of only ~250 ng/mL has been achieved (Guzzo CA et al., 2017)."
"On the basis of the rationale above, any significant antiviral activity could not have been achieved with the dose used in the study and the resultant plasma concentration of the administered ivermectin. Thus, although ivermectin, in vitro, is a potent inhibitor of SARS-CoV-2 replication, in vivo, the plasma concentration required to achieve the antiviral effect far exceeds the therapeutically applicable dose."
This thread discusses why the example of Uttar Pradesh's program isn't good evidence.
> There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake.
Well, the gold standard RCT Recovery (https://www.recoverytrial.net/) had a look.
> The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications.
Dexamethasone is a cheap steroid. (For that matter, vaccines are incredibly cheap and yet nobody seems to have stopped them in favour of, say, monoclonal antibodies.)
> Do you not thin that this incentive influences what gets into the news?
Evidently not terribly much, given that dexamethasone was at least in all the British newspapers.
> Do you think the public health authorities in Uttar Pradesh are lying?
Quite plausibly. UP is perhaps the worst governed state in India and has been under all political parties. The case of Kafeel Khan is rather illustrative.
More to the point, I don’t care whether they’re lying. The whole article is full of vague statements that are hardly a good basis to believe anything about ivermectin.
OK, so weak evidence.
> Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs.
Sure-- weak/crappy evidence and practitioner intuition can definitely point at worthwhile things to study rigorously, even if most of what they generate is trash.
> The evidence for IVM as a treatment for covid (and many other viruses) is quite strong.
??? Quite a leap you made there.
For one, the company that sells ivermectin in the US (Bayer) does not currently have an alternative covid treatment. They have publicly stayed that they do not believe ivermectin helps against covid. Secondly, an RX of ivermectin (for humans) appears to cost more ($35) than the vaccine ($20). Additionally, the vaccine is already paid for, whether or not people use it, many countries (especially the US) pre-purchased hundreds of millions of vaccine doses.
Given that vaccines are already sold and adding ivermectin is pretty safe and is being added to the cocktail of treatments, already being used, I see no financial incentives for drug companies to discourage it.
It's possible, the number of excess deaths in the region over a period (1 July 2020 and 31 March 2021) was measured at 197k compared to other years, but they only reported 4500 covid deaths.
This and
> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians.
> Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs.
and
> Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications.
Don't really add up. Best case interpretation of your argument is that you think doctors are split in half - not wholly aligned behind novel treatments - the "throw shit at the wall and see what sticks" group and the "only throw new custom expensive stuff at it" group, but even that doesn't really match what I'm seeing.
A large number of doctors are out there throwing all sorts of things at a new disease because nobody knows what works yet. The data is going to be incredibly messy. One thing that has looked effective in many cases is steroids, very much not new. Other things that looked potentially effective haven't continued to look effective as more studies have been done.
Where's the massive pushback against steroid treatment if this is an institutional greed thing?
It looks to me much more like some people get married to their early hunches and dig in hard when the evidence doesn't pan out.
Throw enough shit at the wall in enough places and all sorts of false leads are going to appear. Some of them getting shot down isn't a conspiracy. It's how we learn.
Yes.
https://journals.lww.com/americantherapeutics/fulltext/2021/...
Ultimately we need a real large scale controlled trial to settle the issue so I'm looking forward to seeing results from NIH ACTIV-6.
https://www.nih.gov/research-training/medical-research-initi...
This is noteworthy because it's also the only other RCT to show strong effect on mortality (see Fig3 in the two papers).
Original Marik, Kory paper Fig3 is here: https://pubmed.ncbi.nlm.nih.gov/34375047/#&gid=article-figur...
Also, the Nature article is concerned that the underlying data isn't sound due to bad randomization and thus naive meta-analysis is inherently flawed in these cases.
https://www.covid19treatmentguidelines.nih.gov/
In addition to mortality it probably makes sense to look at other endpoints such as patient reported symptoms, RT PCR test cycle count, and time to hospital discharge. Those should allow us to tell if there is a real effect (or not) with smaller subject groups.
Well, sure, but what else is new? The Ivermectin paper was surely bad, but it wasn't outrageously bad nor unexpectedly so. The mania that resulted isn't, at it's core, about bad science. This won't fix the problem.
Oh, yes it was bad. Very very bad. Outrageously bad. The data was mostly fabricated:
https://gidmk.medium.com/is-ivermectin-for-covid-19-based-on...
As these two papers1,6 were the only studies included in that meta-analysis to demonstrate an independently significant reduction in mortality, the revision will probably show no mortality benefit for ivermectin.
This [1] official Mississippi government document says, "At least 70% of the recent calls have been related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers."
But then the AP [2] seemed to say that was incorrect: "The Associated Press erroneously reported based on information provided by the Mississippi Department of Health that 70% of recent calls to the Mississippi Poison Control Center were from people who had ingested ivermectin to try to treat COVID-19. State Epidemiologist Dr. Paul Byers said Wednesday the number of calls to poison control about ivermectin was about 2%. He said of the calls that were about ivermectin, 70% were by people who had ingested the veterinary version of the medicine."
Does anyone have additional clarification?
[1] https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf
[2] https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-live...
(I think eating horse paste is dumb, but that doesn't excuse rolling stone lying about the consequences of doing so.)
The loss of individual bodily autonomy, doctor-patient relationships, and dominion over one's own healthcare is at stake and those won't be easy human rights usurpations to correct.
I thought they said gunshot victims weren't getting treated in some podunk tiny town of less than 10k residents, then they plagiarized a photo to add a racial element, using African Americans, then spread the story everywhere?
https://www.msn.com/en-us/news/us/rolling-stone-covid-19-deb...
• The Mississippi Poison Control Center has received an increasing number of calls from individuals with potential ivermectin exposure taken to treat or prevent COVID-19 infection.
• At least 70% of the recent calls have been related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers.
So, 70% of "calls from individuals with potential ivermectin exposure" were "related to ingestion of livestock or animal formulations of ivermectin", which is what the AP's correction says.
Still, the AP misunderstood as well, misreported it, and later issued a correction. Before the correction, it was syndicated by many news outlets like New York Times. I think most people are unaware of the important correction.
Society is not ready to watch science in realtime.
1. Prevent the viewing 2. Increase the readiness
Of which I think #2 is most preferable.
Once you get below the top N% in intelligence levels (5%-20% in my experience), the ability to 1) understand any kind of complex systems, 2) read, understand, contextualize and retain data, and maintain any rigorous logical thinking structure (e.g., keeping previously eliminated options eliminated) declines rapidly.
The result is that, despite having absolute record numbers and percentages of people educated with college degrees, we have massive anti-science movements that are literally killing thousands of people daily, by ape-ing scientific-sounding terms & distorting concepts & data in order to more effectively broadcast disinformation - and hordes lap it up.
We even have nurses and healthcare workers, who supposedly have been taught and passed tests on basic germ theory, actively resisting and campaigning against safe and effective public health measures.
A related phenomenon is that college degrees are systematically being degraded. I personally know someone who was a visiting professor at a US State University, teaching introductory economics. He found that many of the students didn't even have the math skills (or motivation) to understand and wield the basic concepts on assignments, classroom discussion, and tests, and of course he was recommending them to remedial options and failing them. He was explicitly ordered by the administration to pass them or quit. He quit.
Sadly, it is looking more and more like this great experiment in college for all is not working out as hoped. Instead of a culture of wisdom, we have a culture of sophomores - literally wise fools, who know very little, but think they know it all, and therefore don't have to listen to any expert who actually has real knowledge.
It is considered obvious that at 5'6"/168cm, I was not born with the attributes necessary to engage in a professional basketball career. Yet the same kind of sorting based on intelligence is considered something to not discuss, perhaps getting too close to eugenics.
I strongly believe that the opportunity should exist for any person to get whatever level education they want, without financial or other obstacles. But, with the caveat that it cannot be dumbed-down - either you can understand and do the work and pass, or you do not. The practices seen above, and grade inflation in general need to be reset. The problem is that failing your students is bad for business, so unlikely that most colleges will reform.
The studies on ivermectin seem to be split between "good effect" and "no effect," and there don't seem to be any (by my extremely informal review! going off of memory here) in the camp of "bad effect."
Seems reasonable to take ivermectin as a decent gamble to me while we wait on the dang science to get its head out of its butt.
Thus seeing "no effect" places an upper bound on how good an effect you will see as "none", and a lower bound as "won't kill most people quickly". That's not a good space to gamble into.
It took almost an year until the scientific community settled down that HQC for treating COVID-19 is harmful. The actual formal result is still "no effect and doing more studies is anti-ethical" because nobody can tell exactly how harmful it is. Probably nobody will ever be able to tell (and that's a good thing).
The "bad effect" doesn't have to be strictly medical, and may not show up in studies. It could be that other people who need the medicine can't get it, it could be that it discourages people from getting the vaccine, it could just be that we are lighting a pile of money on fire for no reasons (that's bad, right?).
If you are concerned about wasting money, consider that for one dose of (also unproven!) medication like convalescent plasma you could buy about a thousand doses of generic, cheap drugs like ivermectin. And that has been tried about 500000 times, still is unproven but is not considered controversial.
Could we actually not manufacture enough of it, or were activist pharmacists just refusing to fill prescriptions of it?
After all, unlike iver, there is very good hospitalization data about vaccinated vs unvaccinated now.
Remember that the in vitro study that gets cited a lot used a concentration that would be lethal in humans.
The fraudulent studies (y'know, including dead patients, patients that never existed, drugs that weren't administered and so on) have shown a good effect.
The real studies unfortunately showed no effect.
My advice to you; don't gamble. Ever.
https://www.thedesertreview.com/opinion/columnists/indias-iv...
https://www.thedesertreview.com/news/national/indias-ivermec...
https://www.thedesertreview.com/opinion/columnists/indias-iv...
https://www.thedesertreview.com/opinion/columnists/indias-iv...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968425/
https://journals.lww.com/americantherapeutics/fulltext/2021/...
Ivermectin is safe enough to take, the important question is does it do any good against covid. At best it doesn't hurt you and it's unclear, but probably does nothing. It's certain there is no international pharmaceutical conspiracy trying to block discussion of it. That's different than trying to avoid showing incorrect medical information to people during a worldwide medical emergency. The hospitals in my state are full of idiotic non-vaxed covid victims. The latest thing is a conspiracy that the hospital won't treat them with ivermectin because they want them to die.
People are just killing themselves because of their bizarre and irrational resistance to safe, life-saving vaccinations and preference for random spoutings on the internet to research proven treatments. Do people challenge their math professors in college because they don't consult fox news for the truth? No. I don't have much hope for our future when we can't get these simple things right. It's like a new dark ages has come upon us. But the truth is we humans were always this foolish.
>Safe and effective... Every day that becomes more untrue in highly vaccinated populations like the UK and Israel, whose hospitals and morgues are full of vaccinated people.
https://www.gov.uk/government/publications/investigation-of-...
https://www.gov.il/en/departments/guides/information-corona
There is substantial risk when it comes to mass vaccination in the middle of a pandemic as well, especially with highly infectious and rapidly mutating viruses, coupled with vaccines that are extremely ineffective at preventing spread.
https://www.geertvandenbossche.org/
Calling it "conspiracy claims" doesn't suddenly invalidate the overwhelming amount of empirical evidence.
So India and Africa should absolutely keep using IVM.
In high latitudes similar effect could possibly be had with treating everybody with vitamin D.
Unfortunately the current zeitgeist is to send you home with nothing to wait till your lips turn blue.
When one option has billions of revenue at stake, investors will pay for more/focused studies vs an option to reuse low-cost generics. Unfortunately, or fortunately, desperate humans have skipped trials of both vaccines and early treatments, so there is data on both.
>Regarding Ivermectin, The Desert Review covers it extensively to the point where you would think this is an Ivermectin promotion source. Perhaps it is as nearly every article talks about the positive virtues of Ivermectin such as this Gaslighting Ivermectin, vaccines and the pandemic for profit and this The great Ivermectin deworming hoax. Many pro-Ivermectin opinion articles are written by Justus R. Hope, MD., who admits this name is a pseudonym underneath the articles he writes.
Do you have any criticisms of the actual data or just ad hominems of the source?
Remdesivir has three randomised controlled trials all of which indicate statistically significant effects, and there don't seem to be any credible challenges to these trials results. Currently given the concerns about the irregularities in the data in it's existing trials, Ivermectin has none.
[1] https://www.sciencedirect.com/science/article/pii/S016635422...
However, I've also heard there's a new study coming out from Gilead that demonstrates Remdesivir is highly effective when administered in early treatment.
So perhaps the efficacy depends when treatment is given. And if that's the case, then meta-studies actually become very important, because they can reveal hidden factors like dosage, demographic, when to administer treatment, etc.
For what is worth most meta-study will check if they reach the same results leaving-n out (typically one), but I agree that they could do much better accessing the underlying data itself.
[1] https://www.nature.com/articles/d41591-020-00019-9
Edit: Oops...forgot to link the article. Added.
It's a lot harder to say how a fully vaccinated population will fare compared to a fully unvaccinated population. In the short term the unvaccinated population will certainly fare worse (more sick, more dead), but at a population level they will develop a stronger, longer lasting immunity and exert no mono-directional pressure. While in the fully vaccinated population, as long as the R0 is over 1 (which looks to be the case) the virus will be driven towards escape variants, it might not matter how many more people remain asymptomatic or how many fewer people die when new variants keep driving the pandemic forward and render the vaccines ineffective. It's population-level immunity that ends pandemics, immunity works very different on a population level than on an individual level.
Rather ironically if it turns out that this is indeed the case, then the people getting the vaccine are the "selfish" ones (protecting themselves short term from serious disease/death at the long term cost of the wider population) rather than the ones refusing the vaccine. Of course that's not entirely fair because people are doing it with the best of intentions and not out of "selfishness". I'm pointing this out more to demonstrate that things just aren't as simple as the media likes to portray it, i.e. with the non-vaccinated as the "selfish" ones.
If it turns out that vaccination campaigns do indeed do more harm to the population long-term than good (something we'll likely only know for certain after the pandemic is over or, more likely at this point, has become endemic), then medicine such as Ivermectin, even if only marginally effective at combating COVID starts to look a lot more interesting because it does not exert those same pressures on the virus.
There's several other ways the vaccines could end up hurting us in the long term, such OAS (Original Antigenic Sin) or ADE (Anti-body Dependent Enhancement), although it's looking really good on those fronts right now so I'm not worried about those.
The discourse going on at the moment on in general is really cancerous (even on HN sadly). As much as I find people who believe that there is no virus, or that vaccines are made to kill people, or following health advice from random internet sensations to be ridiculous, I find myself far more worried by the lack of intelligent discussion and the instant demonization and name-calling of anyone who asks questions that are critical of the vaccination campaigns. A large part of that I think is that the anti-vaxxers have been given so much media-attention (negative) that people assume anyone putting forward critical opinions "must be one those" and can be dismissed without notice.
No one knows what time will tell. Maybe this only has a one-in-a-thousand chance of ending up being the case. But I think it would be wise for people pushing for mandates to think about how society will look back at the COVID19 pandemic in say 50 years, if it turns out that the vaccination campaigns had a net-negative long-term effect. Is that really a risk we are willing to take? My take is that it would be wise to keep safe in any way we can: mask up, disinfect, get sun, keep fit, socialize responsibly, etc. And to avoid radical action before the science is settled, and vaccine mandates are radical. Science has a long history of settling on wrong for a while before getting it right, let's give it some time.
But what's that? "anshorei" on HN wants us to stop vaccines, cause clearly that will just cause a super mutation to evolve?
If you believe that, you might just jump off a bridge right now. Because if it's not a COVID mutation, it will just be another virus evolving. They evolve every day! Evolutions big random number generator never stops! Theres a cell multiplying in your body right now, chances are it might just turn into cancer! Is that a risk you are willing to take?
I'm wondering, at what point, if ever, would you decide that the COVID vaccines are safe / worth it? Honest question.
Also, as someone else mentioned here [1], isn't natural immunity plus vaccine-induced immunity considered even better than natural immunity alone? I haven't fact checked this but they said that was also found from one of the Israel studies. Based on this, wouldn't it still make sense to get the vaccine?
You also mentioned the media. Isn't it possible that conservative media is also manipulating the truth for their narrative? 90% of Fox News staff is vaccinated and yet they still cast doubt on the vaccine [2]. Also, Tucker Carlson won't say if he's been vaccinated or not [3], yet he's one of the big proponents telling people not to get vaccinated. I hear this criticism that the media is spreading misinformation, but it seems like if that's the case, we should consider that it could be happening on both sides.
[1] https://news.ycombinator.com/item?id=28617742
[2] https://www.theguardian.com/media/2021/sep/15/fox-news-vacci...
[3] https://www.thedailybeast.com/cnn-host-alisyn-camerota-calls...
I have learned there are many idiots among us. Many, many idiots.
Is this from being incapable of following science and drawing rational conclusions? Or is it more of a tribal thing, where they are exposed to a biased subset of information/misinformation, and are now emotionally invested in the success of ivermectin because their tribe is?
Either way, like someone else in the comments said, these past 2 years have shown us that laypeople are incapable of following active science in real time and drawing reasoned conclusions. Frankly, this is probably true of everyone who is not an expert in the field in question. We need organizations like the CDC and FDA to be much better about their messaging (remember the no-mask debacle? Great way to lose credibility, guys and gals), and we need much better tools to shut down the spread and weaponization of misinformation from the anti-vax crowd et al. I honestly don’t have any idea of how either of those get fixed, however.
Instead, covid threads are awful. Comments which are pure drivel and talking points are the norm. Politics has infested and rotted our brains.
So with ivermectin, it’s as I was with HCQ or Vitamin D: I’m open minded and intrigued. I want to read the studies, especially the theoretical ones. Let me watch things develop and let medicine take it to patients if the science gets there. But you can’t do that when every other comment is weaponized to the point where people are scarred to read articles because they might contradict their dogma.
I've been avoiding HN threads about the COVID like I avoid any scaremongering ones on Reddit: it's just a massive pile of people that think they know better than most spreading constant misinformation.
The worst thing about the pandemic is it has made the vast majority of the populace an expert in epidemiology, biological containment, sociology, politics, economy, virology. Everyone has an opinion to share about it. Everyone has something to say about it.
In a forum where most people are technically-minded, this creates the negative and odious version of nerd sniping. Nerds talking out of their arse about stuff way over their head.
I don't like calling for censorship, but I wish dang would demote and let any COVID-related post slide off the front page 10x as fast as any normal thread. They did it for Bitcoin, and frankly it was not such a shitshow.
You can’t pretend to be searching for truth if your solution to the problem of people making mistakes is to shut down any possible way to discuss the disagreement. I just find the cognitive dissonance on display here staggering. How do you you know you’re right? Have you ever been wrong? I suppose you knew at the time that you were wrong? Or maybe you just know that this time you’re right?
I also never said shut down disagreement. That’s a straw man you created. Anti-vax is not a good-intentioned disagreement with sound scientific merit, it is a pseudo-science movement that actively and knowingly disregards the truth. Scientific freedom and discussion is important. Allowing pseudoscience to flourish under some strange argument that their positions are as scientifically valid as actual science, is, frankly, nonsense.
Strong effect? I read it was a mild antiviral
> and even crazier, that it may be safer or more effective than the mRNA vaccines
It is definitely safer according to the literature
VAERS, even with its data quality issues, is tracking ~7600 deaths from COVID vaccines in the US. VAERS is widely alleged to have large factors of undercounting [1] around vaccine deaths & injuries
> Adverse events from drugs and vaccines are common, but underreported. Although 25% of ambulatory patients experience an adverse drug event, less than 0.3% of all adverse drug events and 1-13% of serious events are reported to the Food and Drug Administration (FDA). Likewise, fewer than 1% of vaccine adverse events are reported. [2]
If VAERS only has 1%, 5%, or 10% of actuals, things are going to get much worse.
However, despite the skyrocketing counts of pericarditis and myocarditis among young men in particular, they are still pushing vaxxes for the youngest that have the lowest death rates from covid.
Really, this is becoming a medical ethics issue of coercion and a violation of Due No Harm.
[1] https://www.bmj.com/rapid-response/2011/10/30/adverse-reacti...
[2] https://digital.ahrq.gov/sites/default/files/docs/publicatio... -- search for under in the document.
Hint: as soon as you know you're right, and you make statements based on that, when you're inevitably wrong (not saying this in a disparaging way - making sense and being right through all this is nearly impossible), you will lose all trust.
I’m not saying no discourse or testing should happen. I’m a scientist, I believe scientific freedom, and of course, that includes a lot of disagreements. But those disagreements happen in the scientific community, not in the general public. What’s happening in the general public is not at all connected to what’s happening in the research.
Instead, I’m interested in how these “treatments” with no strong evidence are getting weaponized by motivated agents (like the anti-vax crowd) to sow distrust both in scientific organizations (the CDC, and the FDA, Pfizer, Moderna, et al), and in the use of tools with proven effectiveness, like the vaccines themselves.
Imagine to oppose a perfectly safe vaccine that has been administered 6 BILLION times all around the world and that has a proven efficacy of at least one order of magnitude against delta variant and to push for a horse dewormer (that bear in mind it’s perfectly effective for what is used for.. killing parasites, not viruses)
I think it’s because a lot of the HN demographic has quite a big overlap with the people that use social networks where all this bullshit originates and it is amplified and it spreads.
At this stage, the safety is fairly quantifiable, too: https://www.publichealthontario.ca/en/health-topics/immuniza... has a weekly adverse effects report which breaks down myocarditis/pericarditis by sex and age, per million population (the most common dangerous side effect for mRNA vaccines).
Who here is opposing vaccines? You've created quite the strawman in your head.
>I think it’s because a lot of the HN demographic has quite a big overlap with the people that use social networks where all this bullshit originates and it is amplified and it spreads.
In other words Ivermectin is a proxy issue in the culture war. Hence why it's so polarizing and people are quick to regress from critical thinking to group think narratives.
I know plenty of anti-vax, some of them remarkably smart, some of them are health professionals.
We are all biased, and overcoming bias is hard. It is a field of expertise by itself, and it is usually not required for tech jobs. Just being smart will only allow you to find more complex but just as fallacious arguments that will confirm your bias. For example, it took me a while to "believe" in climate change, I took a while to realize that solar panels are not just for pocket calculators, and things like that, for a variety of reasons, and found a lot of advanced material to fuel my bias, which still has not completely disappeared. I am not particularly attached to Ivermectin so there is no bias for me to overcome, but I understand that some people can be. Try to think about it yourself, you probably believe in stupid things too.
And getting attached to a cheap treatment for a disease that has been messing with our lives since early 2020 is not what I would consider an unhealthy reaction. It is hope. Getting too attached to it can be a problem, but no matter what we want to think, we are just humans.
These two things are at odds with each other. When the authorities are wrong, contradicting them is classified as "misinformation". If they cannot be contradicted, they are the only people capable of correcting themselves. The results of that will be pretty predictable.
When I heard of the COVID outbreak, I promptly put on my P100 mask and tried to go to sleep in it. Tried being the operative word.
Later on, switched to my N95. Ah yes, the joys of sleep!
To the downvoters: put up or shut up. Your opinion doesn't change the facts.
What would happen if you got to be the contrarian that predicted the experts' wrongness? That would prove you're smart.
And a lot of us want to feel smart. So that makes us more vulnerable to certain cognitive weaknesses.
I am one of those people that would trust Ivermectin more for treating (or prevention) of COVID compared to a mRNA-based vaccine and I have plenty of reasons for thinking so.
Some reasons I would avoid mRNA based vaccines:
- There's plenty of strokes into my family and I worry that I could easily get a stroke as well, perhaps due to genetically smaller arteries in my head (just a hunch). Seems many deaths of mRNA based vaccines were caused by blood clots.
- Looking at the numbers, I really don't believe COVID is very dangerous for most people. COVID is mostly dangerous for obese people, old people, people with co-morbidities and for those people it might make sense to use a vaccine (same we used to do with the flu every year).
- I feel the number of reported deaths are not correct, since in many countries, if people die with COVID, it's reported as a COVID death, while people might have died from e.g. cancer. As such, actual deaths are probably much lower.
- The media's unfair and sensationalist reporting of "horse dewormer" is one of the reasons I don't trust big media anymore (and there's many others in the past as well).
- Overall, Ivermectin is really very safe when using dosages based on body weight. It's cheap and easy to get. It's easy to mass produce. So even if Ivermectin would not work, there's very little risk when using the medicine responsibly.
- I've read many articles and looked at graphs of countries using Ivermectin and to me it seems there's a clear relation with the use of Ivermectin and the reduction in deaths and COVID cases.
- Even if the whole world would take the vaccine, it's very unlikely we'd stop COVID due to immune escape. Several sources already believe COVID is here to stay, like the flu. And I don't wanna bother to take every year a booster for some COVID mutation.
- In my view we can't be sure if the mRNA vaccines are totally safe in the long run. I will wait a couple of years (5 or more) and see if people receive any adverse long term effects. If not, I will be ok to accept mRNA-based vaccines in the future, but not going to take one right now.
- I was actually open to get the (traditional, e.g. weakened or killed off virus) Sinovac vaccine for COVID if it would make movement around easier in Thailand, but since Thailand now wants to combine the Sinovac vaccine with AstraZeneca, I won't bother.
https://c19ivermectin.com/ is a very adequate counter-argument to the article, and it's unfair to the whole scientific community that comments are greyed out that mention it.
Just take it.
J. S. Mill wrote the rebuttal to your argument 160+ years ago. He wasn't using it as an anti-vaxx argument either, so it might be time to stop the moralising and simply try to make a persuasive case. I'd wager it's easier without the moralising anyway.
Factually false.
1. It isn't a vaccine. It's a chemical signal to make your body make things.
2. It doesn't have the efficacy against the plethora of variants that all coronaviruses like the cold continuously create. You can still get COVID-19 after being "fully vaccinated". Human beings lack the technology to vaccinate against coronaviruses, including COVID and the cold.
3. It has caused blood clots. And the proteins created cluster in reproductive organs.
4. There are no long term studies of its effects.
5. If it kills your spouse, you can't sue the manufacturer.
Stop spreading misinformation about this pseudo-vaccine.
https://www.hopkinsmedicine.org/health/conditions-and-diseas...
https://www.cnbc.com/2021/09/21/who-repeats-warning-against-...
There are multiple vaccines too! The Australian regulator recommends against some vaccines for the young and up until recently they were the only ones available.
https://www.health.gov.au/initiatives-and-programs/covid-19-...
I'm sure there are plenty of other reasons - God forbid you might even have a religious objection to vaccines.
It's clearly a safe drug to take in human-designed doses, and it's cheap to produce. Laughing at people for poisoning themselves with "horse dewormer" instead of pointing out that they are turning to the vet store because their access to medicine has been marginalized is sick.
And maybe it does help, I don't know. Unproven != disproven.
Doing one thing but not another doesn't imply you're doing one thing instead of another.
Do you truly believe the people ODing on ivermectin would be lining up for vaccinations if it didn't exist?
https://www.wnycstudios.org/podcasts/otm/segments/how-iverme...
Keep in mind that Ivermectin is being pushed within antivaxers circles as a prophylactic and the true COVID-19 cure, in contrast with all COVID-19 vaccines and even mask mandates.
Thus it's false to claim that this push towards Ivermectin is harmless as, at best, it's pushed as a placebo that empowers vulnerable people to catch and spread the disease, which ultimately means they are harming themselves and everyone around them.
Furthermore, enabling random unproven treatments is on the same level as saying we should stand by and support homeopathic treatments as a valid alternative to vaccines during a pandemic. We don't let people choose between a tetanus shot or a cup of green tea and olive oil when they step on a rusty nail. It doesn't make sense to let them choose between worm meds and a vaccine when it comes to covid.
How many people have been convinced by the supposed effectiveness of Ivermectin and Hydroxychloroquine that they then decided to not get vaccinated?
It's really not as simple as "unproven != disproven".
US Census collect data on reasons for vaccine hesitancy [1]. #1 and #3 are distrust - of vaccines and of government - which anecdotally matches my network. If that's the case, then we should expect that mischaracterizing treatments to promote vaccines [2] would not be very effective, and most Western countries now are leveling off fairly low in their vaccination rates [3]. But rather than more honesty, we're getting more mandates.
I think Dr. John's Cambell's position, of honest assessment, would have been better as the official position [4]. It's hard to imagine how trust could be regained now though without some sort of reckoning.
1. https://www.census.gov/library/visualizations/interactive/ho...
2. https://www.youtube.com/watch?v=_gndsUjgPYo
Edit: we can talk plenty about how bad the US health care system is, but in this case, the actual vaccine, that does a fantastic job of protecting people from COVID, is free in that you don't have to spend a dime out of pocket.
I understand the hesitation Americans have against it, given its lack of availability (I would never consume a medicine made for animals) but from my outside perspective, the issue has been politicized so much that both "left" and "right" Americans get blinded by their views and are not open to even talk about it (it's either, you eat dewormer antivaxxer! or muh freedom!).
I got my two vaccines as soon as I could (I had covid in march 2020 and had a terrible time, and I am totally pro vaccines, shit in Mexico we get a heck of a lot of vaccines haha) but given the safety profile of Ivermectin, I am 100% in favour of people taking it if they get COVID19.
[1] http://educacionensalud.imss.gob.mx/es/system/files/Algoritm...
[2] https://covid19.cdmx.gob.mx/storage/app/media/Articulos/revi...
They're also the ones that pushed Hydroxychloroquine, have connections to the Tea Party, that "demon semen" lady Trump endorsed is associated with them, and they had their leader and their chief of communication arrested due to their participation in Jan 6th.
They're also the reason you'll see Joe Rogan now spreading ivermectin bullshit.
This is disinformation, it turns out. Plenty of doctors are prescribing it. Anyone in the US can go online to one of a dozen telemedicine services and get a prescription for an appropriate dose of ivermectin within hours. This can then be filled at any pharmacy in most states which prohibit pharmacists from refusing to fill prescriptions because they heard on CNN it was for horses. But the media will never report this.
Oh, and the access to this medicine is “marginalized” BECAUSE IT DOESNT WORK TO TREAT COVID. We generally do not expect doctors to prescribe medicine that will not work or is not appropriate for the patients condition. Complaining about their access being marginalized is like complaining that my doctor is marginalizing my access to Ketamine because I don’t need it.
It’s not “corruption” to point that out.
It's also a valid point that unproven and disproven aren't equivalent. While I don't think anyone should take medical advice from political sources or for political reasons (therefore, as far as I'm aware, the well studied vaccines should be preferred to ivermectin by the vast majority of people at this time), I do think that it should be anyone's right to have full bodily autonomy and make whatever choices they want. Mainstream consensus is wrong often enough, e.g. the disastrous food pyramid that contributed to today's obesity epidemic.
I agree with the thrust of your point that the idea that there's some kind of widespread anti-Republican medical discrimination or corruption going on is silly. Just pointing out that how things currently are is not how they ought to be, and that this situation is arguably just a subset of the widely reviled War on Drugs.
It's not like doctors actually always understand what is going on; for example, I think even the precise mechanism of anesthetics isn't well understood yet.
So people volunteer to test a human approved drug for a different application. I don't believe in Ivermectin specifically, but there's nothing fundamentally wrong with that. It's what medicine does, and most researchers at universities don't have a clue either (as we now see in the entire Covid19 comedy).
People are taking the horse formulation because most pharmacists won't even fill an off-label prescription for the drug, which - even if it has no effect on COVID - is safe and taken by a quarter billion people every year.
Let people take it. It's not harmful.
Or, make a big huge deal about people taking it and, well, then it becomes a big huge deal.
Perhaps we just have different general perspectives on the individual and society.
But access to the vaccines here is free and widespread now, so while we could talk all day about problems with access to health care in this country, it doesn't apply here. People may be choosing to distrust the vaccines and thus triggering a shortage of beds and treatment that they themselves will later need.
The whole point of meta analysis is that you have multiple studies of the same experiment.
Why not consider an index that is higher with the number of successful replications and lower of number of replication tries?
